A pilot study: Examining cytoskeleton gene expression profiles in Pakistani children with autism spectrum disorder

Background: Finding effective pharmacological interventions to address the complex array of neurodevelopmental disorders is currently an urgent imperative within the scientific community as these conditions present significant challenges for patients and their families, often impacting cognitive, emotional, and social development. In this study, we aimed to explore non-invasive method to diagnose autism spectrum disorders (ASD) within Pakistan children population and to identify clinical drugs for its treatment.

Aims: The current report outlines a comprehensive bidirectional investigation showcasing the successful utilization of saliva samples to quantify the expression patterns of profilins (PFN1, 2, and 3); and ERM (ezrin, radixin, and moesin) proteins; and additionally moesin pseudogene 1 and moesin pseudogene 1 antisense (MSNP1AS). Subsequently, these expression profiles were employed to forecast interactions between drugs and genes in children diagnosed with ASD.

Methods: This study sought to delve into the intricate gene expression profiles using qualitative polymerase chain reaction of profilin isoforms (PFN1, 2, and 3) and ERM genes extracted from saliva samples obtained from children diagnosed with ASD. Through this analysis, we aimed to elucidate potential molecular mechanisms underlying ASD pathogenesis, shedding light on novel biomarkers and therapeutic targets for this complex neurological condition. (n = 22). Subsequently, we implemented a diagnostic model utilizing sparse partial least squares discriminant analysis (sPLS-DA) to predict drugs against our genes of interest. Furthermore, connectivity maps were developed to illustrate the predicted associations of 24 drugs with the genes expression.

Results: Our study results showed varied expression profile of cytoskeleton linked genes. Similarly, sPLS-DA model precisely predicted drug to genes response. Sixteen of the examined drugs had significant positive correlations with the expression of the targeted genes whereas eight of the predicted drugs had shown negative correlations.

Conclusion: Here we report the role of cytoskeleton linked genes (PFN and ERM) in co-relation to ASD. Furthermore, variable yet significant quantitative expression of these genes successfully predicted drug-gene interactions as shown with the help of connectivity maps that can be used to support the clinical use of these drugs to treat individuals with ASD in future studies.